A novel MHC-associated Proteinase 3 peptide isolated from primary chronic myeloid leukaemia cells further supports the significance of this antigen for the immunotherapy of myeloid leukaemias

Three of the most promising antigens for immunotherapy of chronic myelogenous leukaemia (CML) include the specific fusion-protein, Bcr/Abl, and the overexpressed proteins WT1 and Proteinase

3. The clinical significance of Proteinase 3 as a target in myelogenous leukaemias has been bolstered by detection of high frequencies of cytotoxic CD8+ lymphocytes specific for this antigen

in patients undergoing immune therapies. Our investigation aimed to directly identify MHC-ligands derived from these antigens and presented on CML blasts by means of affinity-purification

and mass spectrometric peptide-sequencing. Although no known or potential new epitopes were discovered for Bcr/Abl or WT1, a novel peptide from Proteinase 3 was detected among the more

abundant MHC-ligands. Additionally, MHC-ligands derived from known immunogenic proteins overexpressed as a result of Bcr/Abl transformation were also identified. Our investigation is the

second of only a small number of studies to identify a peptide from Proteinase 3 among the more abundant MHC-associated peptides and thus implies that peptides from this antigen are among

the more abundantly presented of the known leukaemic antigens. Taken in conjunction with clinical observations of functional Proteinase 3 specific CTL in patients’, these data further

support the application of this antigen as an immunotherapeutical target for myelogenous leukaemias.

The authors would like to acknowledge Drs J Tolson and M Deeg for their assistance with the interpretation of peptide fragmentation spectra and HPLC-analysis. This work was partly supported

by the European Commission; projects Outcome and Impact of Specific Treatment in European Research in Melanoma [OISTER], (contract: QLG1-CT-2002-00668) and European Network for the

Identification and validation of antigens and biomarkers in cancer [ENACT], (contract: 6FP-CT-503306). We would like to thank Dr Ken Mills for the BCR-ABL transcript analysis.

Present address: PANATecs GmbH, Ob dem Himmelreich 7, 72074, Tübingen, Germany

Present address: Glycotope GmbH, Robert-Rössle-Str. 10, 13125, Berlin, Germany

Section for Transplantation Immunology and Immunohaematology, University Hospital Tübingen, ZMF, Waldhörnlestrasse 22, Tübingen, Germany

Department of Immunology, University Tübingen, Auf der Morgenstelle 15, Tübingen, Germany

Department of Haematological Medicine, King's College London School of Medicine, The Rayne Institute, London, UK

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